Non-invasive in-vivo BBB imaging: APOE4 and WM aging in US minority population - Abstract The E4 allele of apolipoprotein E (APOE4), which is the main genetic risk factor for sporadic Alzheimer’s disease (AD), leads to the breakdown of blood brain barrier (BBB) in the medial temporal lobe (MTL) and is associated with cognitive decline. Mounting evidence suggests BBB breakdown as an event preceding symptomatic stages of AD and other neurodegenerative diseases. Nonetheless, the current scientific field lacks an established, non- invasive technique dedicated to measure BBB integrity, limiting in-depth investigations on how the BBB interacts with various neurobiological factors. While dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) remains the most widely utilized for studying BBB integrity, it is often restricted to patients with symptomatic conditions due to its invasive nature by injecting gadolinium-based contrast agents. The non-imaging alternative to assess BBB integrity relies on cerebrospinal fluid-based biomarkers to reflect overall changes in the central nervous system, which is also invasive and undesirable for non-pathological populations. Here we propose to use a novel MRI sequence, multi-delay arterial spin labeling (ASL) with a T2 preparation (T2prep-ASL), to capture subtle changes in the BBB in genetically AD-susceptible, ethnic minority cohort, where longitudinal and multi-domain biomedical data is also available. Currently existing peripheral blood/serum biomarkers have been proposed as a marker of BBB integrity, however, interpretations on these blood biomarkers require further evaluation in different disease populations due to varying disease progression and need secondary validation for better specificity to BBB status. We will also validate non-imaging markers with the novel BBB imaging measure. On top of the novel imaging technique, we will expand a previously established computational network analytical framework with BBB imaging marker and study systematic changes observed in APOE4 carriers compared to non-carriers. The proposed project will further elucidate the role of APOE4 and BBB in cognitive aging in this unique stateside Puerto Rican population. Successful outcomes will critically support the development of efficient imaging biomarkers, increase our understanding on AD pathogenesis, and reduce health disparities among populations with diverse ethnic and genetic backgrounds. Final goal of the study also aims at developing a network-guided prediction model of BBB status leveraging concepts of latent network modeling.
